Mechanisms of high-density lipoprotein reduction after probucol treatment: Changes in plasma cholesterol esterification/transfer and lipase-activities

Giulia Chiesa, Silvia Michelagnoli, Michela Cassinotti, Gemma Gianfranceschi, JoséP Werba, Franco Pazzucconi, Cesare R. Sirotori, Guido Franceschini

Research output: Contribution to journalArticle

Abstract

Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo) A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma.

Original languageEnglish
Pages (from-to)229-235
Number of pages7
JournalMetabolism
Volume42
Issue number2
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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    Chiesa, G., Michelagnoli, S., Cassinotti, M., Gianfranceschi, G., Werba, J., Pazzucconi, F., Sirotori, C. R., & Franceschini, G. (1993). Mechanisms of high-density lipoprotein reduction after probucol treatment: Changes in plasma cholesterol esterification/transfer and lipase-activities. Metabolism, 42(2), 229-235. https://doi.org/10.1016/0026-0495(93)90041-L